Low-lead exposure in childhood associated with worse cognitive performance [Pediatrics Classics Series]

Classics Series, Landmark Trials in Medicine

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1. Among children exposed to lead early in life, serum lead levels at 24 months of age were significantly associated with decreased cognitive performance on measures of intelligence and educational achievement at 10 years old.

2. Each 0.48 μmol/L (10 μg/dL) increase in serum lead at 24 months of age was associated with a 5.8 point decline in a measure of intelligence quotient and an 8.9 point decline in educational achievement score during cognitive testing at 10 years of age.

Original Date of Publication: December 1992

Study Rundown: At the time of this publication, prior studies investigating early, low-level lead exposure and cognition later in life had mixed findings. Previous reports assessed the potential connection between lead levels and cognitive performance into preschool years. This was the first study to investigate the effects of early low-level lead exposure on cognitive performance into school age. One hundred forty-eight children were assessed from birth to 10 years of age for serum lead levels and cognitive development through intelligence quotient (IQ) testing via the Wechsler Intelligence Scale for Children-Revised (WISC-R) and the Kaufman Test of Educational Achievement Brief Form (K-TEA). Findings indicated that serum lead levels at 24 months of age were significantly associated with IQ and neuropsychiatric performance at 10 years old, a finding which was upheld after controlling for covariates. There is no known reason as to why children are most vulnerable to lead toxicity in this specific time frame. This study was limited by the potential role of bias towards children available for follow-up as multiple participants were lost from 5 years of age to 10 years old. In addition, this cohort was of higher socioeconomic status (SES) and intelligence than the average citizen, which may have allowed for an enhanced view of the cognitive effects of lead, but makes the findings less generalizable compared to previous study cohorts of lower SES who were more likely to be exposed to environmental lead. This study indicated that even at low levels, early lead exposure is linked to poor cognitive development through school age. Combined with previous work, these findings encouraged the Centers for Disease Control to lower the benchmark for toxic lead levels to the current 0.24 μmol/L or 5 μg/dL.

Click to read the study in Pediatrics

In-Depth [prospective cohort study]: Two hundred forty-nine infants born between August 1979 and August 1981 were recruited from Brigham and Women’s Hospital in Boston, Massachusetts with umbilical blood lead levels in the ranges required for eligibility. Infants were considered for study inclusion if their umbilical cord blood lead levels were below the 10th percentile at the time of the study (< 0.15 μmol/L or 3 μg/dL), around the 50­th percentile (0.31 μmol/L or 6.5 μg/dL), or above the 90th percentile (> 0.48 μmol/L or 10 μg/dL) indicating, respectively, “low,” “medium,” or “high” prenatal lead exposure. Infants’ lead levels and development were evaluated at 6, 12, 18, 24, and 57 months of age and then again at 10 years old. Primary cognitive outcomes were assessed through the use of the WISC-R and K-TEA.

Of the initial cohort, 148 children were included in the final analysis as they completed the entire study course. Of those, 116 had serum lead measurements at all 7 time points, including birth (mean 0.14 μmol/L or 2.9 μg/dL). Multiple regression analysis was completed with appropriate adjustment for confounders. Overall, participants had cognitive scores about 1 SD above the national average. After controlling for covariates, only the lead levels of children at 24 months of age (mean lead level < 0.34 μmol/L or < 7 μg/dL) were significantly associated with cognitive performance including the full-scale WISC-R IQ and K-TEA battery composite. Each 0.48 μmol/L (10 μg/dL) increase in serum lead was associated with a 5.8 point decline in the IQ measure and 8.9 point decline in the K-TEA composite (p < 0.01, p < 0.001, respectively). No significant association between lead levels and cognitive scores was seen at any other age.

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